Aims and Scope Translational Andrology and Urology (TAU; Transl Androl Urol; Print ISSN 2223-4683; Online ISSN 2223-4691; http://tau.amegroups.com) is an open access, peer-reviewed and monthly journal that covers various aspects in diseases of male and female urinary tract including kidneys, ureters, bladder and urethra and the male reproductive organs like penis, testes, scrotum, prostate, etc. TAU is indexed in PubMed/PubMed Central (PMC), Scopus and Web of Science [Science Citation Index Expanded (SCIE)] and its latest impact factor for TAU is 1.9. Meanwhile, TAU is endorsed by the Genitourinary Medical Association of China International Exchange and Promotive Association for Medical and Health Care (GUA-CPAM). The entire submission and review process are managed through OJS system, an electronic system, which provides an efficient way and ensures a rapid turnaround of papers submitted for publication. Articles will be published both in print and online. See more at Information for Authors. TAU is published by AME Publishing Company, with support from Wolters Kluwer (the journal content will be made available on Wolters Kluwer Health’s Lippincott and Ovid platforms). Indexing Translational Andrology and Urology is indexed and covered by Web of Science [Science Citation Index Expanded (SCIE)] PubMed PubMed Central (PMC) Scopus Google Scholar Medscape MDlinx Ovid Information for Authors TAU is a member of Committee on Publication Ethics (COPE) and it follows the Committee on Publication Ethics (COPE)'s guidelines and the ICMJE recommendations for the Conduct, Reporting, Editing, and Publication of Scholarly Work in Medical Journal. Manuscripts submitted must be the original work of the author(s) and must not be published previously or under consideration for publication elsewhere. Manuscripts Turnaround Time In-house review: 1-3 weeks. External peer review: 1-3 months. Publication Ahead of Print: within 1 month after being accepted (with APC payment received). Formal publication: within 1-3 months after being accepted (with APC payment received). Original Articles are listed as priority. TAU is the Official Publication of: Society for Translational Medicine (STM), Hong Kong Publication Schedule Published quarterly from Mar. 2012 to Dec. 2014 and bimonthly from Jan. 2015 to Dec. 2020, TAU now follows a monthly publication model. Open Access Statement This journal is a peer reviewed, open access journal. All content of the journal is published under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0). All articles published open access will be immediately and permanently free for all to read, download, copy and distribute as defined by the applied license. Free access and usage Permitted third party reuse is defined by the CC BY-NC-ND 4.0 license. This license allows users to copy and distribute the article, provided: this is not done for commercial purposes and further does not permit distribution of the Article if it is changed or edited in any way. the user gives appropriate credit (with a link to the formal publication through the relevant DOI) and provides a link to the license but not in an any way implying that the licensor is endorsing the user or the use of the work. no derivatives including remix, transform, or build upon the material was allowed for distribution. The full details of the license are available at https://creativecommons.org/licenses/by-nc-nd/4.0/ Copyright For open access publishing, this journal uses an exclusive licensing agreement. Authors will transfer copyright to AME Publishing Company, but will have the right to share their article in the same way permitted to third parties under the relevant user license, as well as certain scholarly usage rights. For any inquiry/special circumstance on the copyright, commercial usage or adaptation of TAU articles, please contact: permissions@amegroups.com For reprint order, please contact: sales@amegroups.com Support for Authors to Comply with Funding Body Mandates We work with authors of research articles supported by funding bodies with open access mandates to ensure that authors can meet their funders’ requirements for public access to research results. In addition, we offer further support for authors who are required to comply with funding body mandates, including but not limited to: All articles published open access will be immediately and permanently free for everyone to read, download, copy and distribute. If a specific open access license is needed, please contact the editorial office for confirmation before submission. Example of statements in a published article: https://jgo.amegroups.org/article/view/76355/html. No copyright is claimed for any work of the U.S. government. Example of statements in published articles: https://actr.amegroups.org/article/view/8875; https://med.amegroups.org/article/view/8358/html. Contact with Editorial Office Mira Wu, Corresponding Editor, Translational Andrology and Urology Email: tau@amepc.org Publisher Information TAU is published by AME Publishing Company. Address: Hong Kong branch office: Flat/RM C 16F, Kings Wing Plaza 1, NO. 3 on Kwan Street, Shatin, NT, Hong Kong, China. Updated on July 10, 2026
An argument not to EMBARK on systemic therapy for biochemical recurrence of prostate cancer
Neoadjuvant chemotherapy in upper tract urothelial carcinoma: interpreting durable long-term outcomes in a changing treatment landscape
Rural-urban disparities in high‑risk non-muscle‑invasive bladder cancer: lessons from the Canadian Bladder Cancer Information System
Results from the PRESERVE trial: an editorial commentary
Redefining the standard of care for high-risk biochemical recurrence of prostate cancer after definitive therapy: insights from the EMBARK final analysis
The modified Whitaker test is a reliable adjunctive rule-out tool for evaluating efficacy after ureteral reimplantation
Background: Ureteral reimplantation (UR) is the standard treatment for distal ureteral stricture, yet postoperative anastomotic restenosis impairs outcomes, with conventional imaging unable to quantify urinary tract obstruction and dysfunction. This study aimed to explore the clinical value of the modified Whitaker test in ruling out upper urinary tract obstruction and assisting postoperative efficacy evaluation after UR. Methods: A total of 100 patients (105 renal units) who underwent UR from January 2022 to December 2025, with preoperative nephrostomy tube placement and postoperative modified Whitaker test, were prospectively enrolled. Combined standing and supine position examination, gradient perfusion (5~25 mL/min) pressure measurement combined with imaging development classification was used. Patients were classified into three types based on the pyelovesical pressure difference and ureteral peristalsis. Perioperative and follow-up data were collected to evaluate the curative effect. Results: Among patients undergoing modified Whitaker test after UR, 73 cases (69.52%) were Type I, 24 cases (22.86%) Type II, and 8 cases (7.62%) Type III. The median follow-up time was 12.63 (6.92, 25.80) months. The overall surgical efficacy rate was 92.38% (97/105), and the objective efficacy rate was 98.10% (103/105). In the modified Whitaker test, the median intrapelvic pressure was 20.00 (16.00, 25.50) cmH2O, the median intravesical pressure was 14.00 (9.50, 20.00) cmH2O, and the median pressure difference was 5.00 (2.00, 9.00) cmH2O. The unobstructed results of the modified Whitaker test were consistent with successful overall postoperative efficacy in 85.71% (90/105) of renal units and with successful objective postoperative efficacy in 91.43% (96/105) of renal units. All patients successfully completed the modified Whitaker test without any postoperative discomfort. Conclusions: UR the modified Whitaker test exhibits excellent negative predictive performance and favorable consistency with mid-term postoperative follow-up outcomes. It serves as a reliable adjunctive tool for ruling out upper urinary tract obstruction and guiding nephrostomy tube removal after UR.
Global research trends in the comorbidity of erectile dysfunction and premature ejaculation: a 20-year bibliometric analysis [2005–2025]
Background: Erectile dysfunction (ED) and premature ejaculation (PE) frequently co-occur, presenting a significant clinical challenge in male health. However, existing research remains fragmented, lacking a systematic overview of the field’s developmental trajectory, knowledge structure, and future trends. This study aims to systematically map the research landscape of ED/PE comorbidity over the past two decades [2005–2025] using bibliometric methods, revealing its evolutionary pathways, research hotspots, collaborative networks, and emerging frontiers. Methods: Based on the Web of Science Core Collection (WoSCC) database, 1,089 ED/PE comorbidity-related publications were retrieved and analyzed. Tools including VOSviewer, CiteSpace, and Bibliometrix were employed for quantitative analysis and visualization of countries, institutions, authors, journals, keywords, and citation networks. Results: Findings indicate: (I) annual publication volume exhibits exponential growth, with pivotal inflection points occurring in 2008 and 2021. (II) China leads in publication output, whereas Italy and the United States dominate academic influence and international collaboration. (III) Research themes evolved through three phases: epidemiology and disease definition [2005–2013], combination therapies and mechanism exploration [2014–2020], and diversified integrated interventions [2021–2025]. (IV) Cognitive behavioral therapy, pathophysiological mechanisms, and emerging physical therapies represent current frontiers, whereas patient psychological counseling and endocrine regulation remain relatively peripheral. Conclusions: This study presents the first knowledge map of ED/PE comorbidity research, revealing a clear trajectory from isolated disease perspectives toward integrated comorbidity models. Future research should deepen exploration of “neuro-vascular-psychological” integrated mechanisms, strengthen high-quality clinical trials, and address current research gaps to advance clinical practice to precision.
USP5 silencing inhibits the proliferation of bladder cancer cells and induces cell apoptosis and ferroptosis by destabilizing COL14A1 expression
Background: Bladder cancer (BC) remains a prevalent malignant tumor of the urinary system with high morbidity and mortality rates. Despite advances in therapeutic strategies, the underlying molecular mechanisms driving BC progression are not fully understood, necessitating the identification of novel biomarkers and therapeutic targets. Ferroptosis, a form of regulated cell death driven by iron-dependent lipid peroxidation, has emerged as a critical player in tumor suppression. However, the specific roles of ferroptosis-related genes and their regulatory mechanisms in BC progression require further elucidation. The study aimed to analyze ferroptosis-related genes and their regulatory mechanisms in BC progression. Methods: This study integrated bioinformatics analysis with experimental validation. Differentially expressed genes (DEGs) between BC and normal tissues were identified using The Cancer Genome Atlas (TCGA) and GSE13507 datasets. These DEGs were intersected with ferroptosis-related genes to screen potential candidates. Weighted gene co-expression network analysis (WGCNA) was employed to identify hub modules associated with BC phenotypes, followed by least absolute shrinkage and selection operator (LASSO) regression and support vector machine recursive feature elimination (SVM-RFE) algorithms to pinpoint key genes. Ubiquitination-related databases were utilized to predict upstream regulators. In vitro and in vivo experiments, including co-immunoprecipitation (Co-IP), ubiquitination assays, functional assays (proliferation, apoptosis, and ferroptosis markers), and xenograft mouse model assay, were conducted to validate the molecular mechanisms and biological functions. Results: Through integrated analysis, 84 ferroptosis-related DEGs were identified. WGCNA and machine learning algorithms further screened and identified collagen type XIV alpha 1 chain (COL14A1) as a critical hub gene. Functional enrichment analysis indicated that these genes were primarily involved in extracellular matrix organization and cell division. Mechanistically, COL14A1 was predicted and validated as a substrate of the deubiquitinase ubiquitin specific peptidase 5 (USP5). USP5 was found to be upregulated in BC cells and interacted with COL14A1 to inhibit its ubiquitination, thereby stabilizing its protein expression. Functional experiments demonstrated that USP5 knockdown significantly promoted COL14A1 degradation, leading to suppressed cell proliferation, induced apoptosis, and increased accumulation of reactive oxygen species (ROS), malondialdehyde (MDA), and Fe2+, while decreasing glutathione (GSH) levels. Crucially, the effects induced by USP5 silencing were effectively reversed by COL14A1 overexpression. In vivo studies further confirmed that USP5 knockdown inhibited tumor growth and reduced COL14A1 expression. Conclusions: This study unveiled a novel USP5/COL14A1 regulatory axis that promotes BC progression by inhibiting ferroptosis and apoptosis. These findings highlight USP5 and COL14A1 as promising therapeutic targets.
Environmental hazards and the risk of development of idiopathic urethral strictures
Background: Though idiopathic urethral strictures are a common form of strictures, little is understood about the pathophysiology leading to their development. This retrospective cohort study sought to analyze the risk of environmental toxins on the development of stricture disease. Methods: Using the Utah Population Database (UPDB), we identified patients with idiopathic urethral strictures born between 1996–2021. Each case was matched 1:1 with controls, based on year of birth and location. Models compared historical air pollution exposure data between the cohorts. Environmental exposures were analyzed in the prenatal period, the first year of life, and the 5 years prior to diagnosis and individual exposures were weighted by the risk of stricture development. Results: We identified 2,048 patients with urethral strictures, diagnosed between 1996 and 2021 and were matched to 1,939 controls for a total cohort of 3,987 men. There was no difference in risk of stricture development for exposure prenatally and within the 5 years prior to diagnosis. The relative risk of cumulative exposures in the first year of life was 1.21 (1.07–1.36, P=0.002) in the development of stricture disease. On univariate analysis, the toxins most associated with stricture development within the first year of life were ethylbenzene, tetrachloroethylene, and molybdenum trioxide. Conclusions: Idiopathic urethral stricture is a common presentation of anterior urethral stricture disease (aUSD) but the mechanism is not well understood. Environmental exposures within the first year of life were associated with an increased risk of the development of a stricture, indicating a potential role within broader inflammatory pathways associated with urethral strictures.
Clinical benefits, tolerability, and risk factors of adjuvant nivolumab for muscle-invasive bladder cancer
Background: In recent years, perioperative-sequential therapies have arisen for muscle-invasive bladder cancer (MIBC) treatment strategies. We are able to select more variable regimens for bladder cancer patients. This study aims to compare clinical outcomes in patients with MIBC who underwent robot-assisted radical cystectomy (RARC) followed by adjuvant nivolumab versus those who did not receive it. Methods: This retrospective single-center study included 60 patients with MIBC who underwent RARC between January 2017 and September 2025. Thirty patients who received adjuvant nivolumab (Nivo group), and 30 patients who did not (no-Nivo group). Disease-free survival (DFS), cancer-specific survival (CSS), and immune-related adverse events (irAEs) were evaluated. Survival analyses were performed using Kaplan-Meier curves and Cox proportional hazards regression models. Inverse probability of treatment weighting was used to adjust for baseline characteristics. Results: Median DFS was significantly longer in the Nivo compared with no-Nivo group [26.0 vs. 9.4 months, respectively; adjusted hazard ratio (aHR): 0.44; 95% confidence interval (CI): 0.22–0.88; P=0.02]. However, CSS did not differ significantly between them (aHR: 0.40; 95% CI: 0.14–1.10; P=0.08). Multivariable analysis identified ≥ pT3, pN+, and absence of nivolumab therapy as independent risk factors for poor DFS. Notably, pN+ remained a significant predictor of shorter DFS even in patients receiving nivolumab (aHR: 4.22; 95% CI: 1.19–15.1). irAEs occurred in 36.6% of patients in the Nivo group, with 13.3% experiencing grade ≥3 events, and three patients discontinued treatment due to toxicity. Conclusions: Adjuvant nivolumab significantly improved DFS in patients with high-risk MIBC in real-world practice; however, patients with pN+ remained at high risk for recurrence despite nivolumab, suggesting the need for more intensive therapeutic strategies in this subgroup.
Thiram inhibits human sperm motility and capacitation by increasing mitochondrial O2− and reducing PTK and PAK4 activity at environmental concentrations
Background: Environmental chemicals may suppress sperm motility (SM), hyperactivation, and capacitation, thus contributing to male infertility. This investigation was designed to examine the impacts of thiram on human SM and capacitation. Methods: We incubated the fungicide thiram with normal human spermatozoa to investigate sperm metrics. Results: Thiram markedly suppressed SM and hyperactivation, demonstrating half maximum effective concentration (EC50) values below 5 µM. In addition, thiram reduced intracellular reactive oxygen species (ROS) and H2O2 with EC50 values of 0.89 and 1.4 µM, respectively, while mitochondrial O2− levels were markedly elevated (EC50 0.9 µM), indicating selective disruption of mitochondrial redox balance rather than general ROS inhibition. It markedly increased mitochondrial O2− with an EC50 value of 0.9 µM. Sperm DNA fragmentation remained unaffected at concentrations up to 10 M. The thiram-induced reduction in SM and forward motility (FM) was proven to be irreversible. Neither forskolin, 8Br-cAMP, pentoxifylline, progesterone, vitamin E (VE), nor A23187 was capable of preventing the thiram-induced decline in SM and FM. Thiram suppressed spontaneous capacitation processes. Additional investigation revealed that thiram reduced tyrosine protein kinase (TPK) levels with an EC50 value of around 0.27 µM, decreased p21-activated kinase 4 (PAK4) levels with an EC50 value of around 0.69 µM, and induced mitochondrial structural damage in normal sperm at concentrations as low as 2.5 µM. Conclusions: Thiram causes irreversible inhibition of human SM, FM, and capacitation through elevation of mitochondrial superoxide anion levels and reduction of TPK and PAK4 activity, and may also act downstream of cAMP signaling, while compromising mitochondrial ultrastructural integrity.
Associations between circulating sex hormones and anterior urethral stricture disease
Background: The pathophysiology of anterior urethral stricture disease (aUSD) is unknown (idiopathic) in the majority of men. Testosterone is required for the in utero development of the male urethra and has been shown to aid in urethral healing. Thus, the purpose of this study was to understand the relationship between circulating sex hormones and aUSD. Methods: This study included 154 males with aUSD undergoing urethroplasty who were enrolled in a prospective, multicenter study evaluating the relationship between inflammation and urethral strictures. This study represents a secondary analysis on serum, measuring circulating levels of total testosterone (TT), free testosterone (fT), estradiol (Es), progesterone (Pr), and cortisol (Co). The control group consisted of males (n=9) lacking urologic pathology undergoing vasectomy. Within the stricture cohort, we looked at differences in sex hormone levels by stricture features and inflammation. T-tests and one-way analysis of variance were used to compare means. Univariate logistic regression was used to assess significant differences followed by multivariable logistic regression to adjust for confounders. Results: fT was lower in the stricture cohort versus control cohort (1.08 vs. 2.13 pg/dL, P=0.05). Adjusting for confounding factors including age, there was a significant decrease in the odds of stricture with increasing fT levels (adjusted odds ratio: 0.33, P=0.02), with a 1-unit increase in fT being associated with a 67% decrease in the adjusted odds of aUSD. Among the stricture cohort, longer strictures were associated with lower fT (P=0.01). Other circulating hormones, including TT, were not statistically different between cohorts or related to aUSD inflammation. Conclusions: We show an association between lower fT, aUSD, and aUSD severity. Bioavailable testosterone is necessary for male urethral development and has anti-inflammatory and anti-fibrotic properties. We hypothesize that fT may contribute to aUSD development by impairing healing to sub-clinical trauma.
Efficacy and safety of oral pentoxifylline on semen parameters and reproductive hormones in idiopathic male infertility: a systematic review and meta-analysis
Background: Male infertility accounts for nearly half of infertility cases, with abnormal semen quality being a major cause. Pentoxifylline (PTX), a methylxanthine derivative with antioxidant and anti-inflammatory properties, has been proposed to improve semen parameters, but evidence remains inconsistent. This systematic review and meta-analysis aimed to assess the efficacy and safety of oral PTX supplementation compared with placebo in improving semen parameters and reproductive hormone profiles in infertile men. Methods: PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from inception to July 2025. Randomized controlled trials (RCTs) comparing oral PTX with placebo in infertile men were included. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Primary outcomes included semen parameters (sperm concentration, total motility, morphology, semen volume). Secondary outcomes comprised serum hormones [testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH)]. Data were pooled calculating mean difference (MD) with 95% confidence intervals (CIs). Results: Five RCTs involving 455 participants were included. PTX dosages ranged from 800 to 1,200 mg/day, with treatment durations of 3 to 6 months. PTX supplementation correlated with increased total sperm motility (MD =10.44, 95% CI: 3.57–17.30) and normal morphology (MD =3.86, 95% CI: 1.01–6.71). Sperm concentration transiently improved at 3 months but did not differ significantly from placebo at 6 months. No significant differences were observed in testosterone (MD =0.22, 95% CI: −0.23 to 0.67) or FSH (MD =−1.51, 95% CI: −4.16 to 1.14) levels, whereas LH decreased marginally (MD =−0.97, 95% CI: −1.45 to −0.49). Reported adverse events were predominantly mild and gastrointestinal. Conclusions: PTX supplementation appears to enhance sperm motility and morphology in infertile men with a favorable safety profile. Its effects on sperm concentration and reproductive hormones are less consistent, and evidence on ultimate clinical effectiveness regarding pregnancy and live birth rates remains unproven. Larger, high-quality trials with reproductive endpoints are needed to clarify its clinical role.
HOXC4 as a machine learning-derived immune biomarker for predicting treatment and prognosis in prostate cancer patients
Background: Prostate cancer (PCa) remains a prevalent male malignancy, imposing significant health burdens and socio-economic challenges globally. While early diagnosis is critical for effective intervention, current clinical strategies lack precision in risk stratification and treatment response prediction. This study aimed to identify key machine learning-derived biomarkers for PCa and to comprehensively evaluate the diagnostic, prognostic, and immune-related significance of HOXC4. Methods: In this study, we integrated 258 samples from four Gene Expression Omnibus (GEO) datasets to identify differentially expressed genes (DEGs) between tumor and normal tissues. Robust feature selection was performed using the intersection of least absolute shrinkage and selection operator (LASSO) regression, random forest, and support vector machine recursive feature elimination (SVM-RFE) algorithms. Ten machine learning models were constructed, with the optimal model interpreted using SHapley Additive exPlanations (SHAP) analysis. These findings were further integrated with gene set enrichment analysis (GSEA), CIBERSORT-based immune infiltration analysis, independent external validation in the Memorial Sloan Kettering Cancer Center (MSKCC) cohort, and pan-cancer analysis. Results: A total of 123 DEGs were identified, from which five key feature genes (RAB17, FAM107A, COL9A1, HOXC4, and TRPM4) were selected. Among the ten models, Partial Least Squares (PLS) exhibited superior diagnostic performance, with an area under the receiver operating characteristic curve (AUC) of 0.977. SHAP interpretation highlighted HOXC4 as a positive risk-associated feature and prognostic candidate. High HOXC4 expression was associated with poor progression-free survival (P=0.02), and this prognostic association was further validated in the independent MSKCC cohort. GSEA indicated that HOXC4-high phenotypes were enriched in cellular energy metabolism and protein processing pathways, whereas HOXC4-low phenotypes showed immune-related enrichment patterns. Immune infiltration analysis suggested that high HOXC4 expression was associated with an immunosuppressive tumor microenvironment characterized by increased regulatory T cell and M2 macrophage infiltration. HOXC4 also showed significant correlations with several immune checkpoint molecules, including CD40 and SIGLEC-15. Furthermore, pan-cancer analysis validated the heterogeneous expression patterns of HOXC4 across diverse tumor types. Conclusions: Identified via interpretable machine learning, HOXC4 serves as a promising diagnostic and prognostic biomarker linked to immune suppression and metabolic reprogramming. This study highlights the potential of combining machine learning-driven feature selection with biological validation to optimize personalized management in PCa.
Machine learning-derived mast cell-associated angiogenesis features can serve as prognostic targets for clear cell renal cell carcinoma
Background: In clear cell renal cell carcinoma (ccRCC), mast cell activation and angiogenesis are crucial for disease progression, with interactions occurring between these processes. The involvement of mast cell-related angiogenic characteristics in ccRCC is not yet fully elucidated. To address this gap, this study aims to clarify the biological role and prognostic significance of mast cell-mediated angiogenesis in ccRCC, and to examine its links to the tumor microenvironment and disease progression. Methods: We utilized bioinformatics techniques to integrate and analyze single-cell and bulk transcriptomics data. We developed prognostic models using ten classical machine learning algorithms and conducted intergroup differential gene extraction, functional pathway enrichment, immune infiltration, and somatic mutation analyses. Finally, the expression levels of the model genes were verified by quantitative real-time polymerase chain reaction (qRT-PCR). Results: TNF-α signaling is significantly upregulated in mast cells within the ccRCC microenvironment, shaping an immunosuppressive microenvironment through receptor-ligand interactions such as SPP1-CD44 and CLEC2C-KLRB1. We developed a mast cell-associated angiogenesis score that demonstrates satisfactory accuracy in assessing prognosis for ccRCC patients. Patients in the high-risk group exhibited activation of oncogenic signaling pathways including JAK-STAT3, accompanied by immunosuppressive status and elevated genomic instability. Furthermore, we identified the core oncogene TIMP1 and the protective gene EMCN. Conclusions: Mast cell-associated angiogenesis features aid in prognostic assessment for ccRCC patients, with TIMP1 and EMCN representing potential therapeutic targets.
Development and internal validation of a noninvasive predictive model based on iron and fat measurements for pathologic risk stratification in prostate cancer
Background: Pathological risk stratification of prostate cancer (PCa) guides treatment decisions. Preoperative noninvasive assessment of PCa risk stratification holds promise for reducing unnecessary invasive biopsies. Elevated levels of iron and fat, along with metabolic disorders in PCa significantly correlate with tumor proliferation and aggressiveness, yet its predictive value in risk stratification remains unclear. We aimed to noninvasively measure fat content as well as iron deposition of PCa lesions by multiparametric magnetic resonance imaging (mpMRI) and investigate their effectiveness in predicting PCa risk. Methods: We prospectively collected patients suspected of PCa with preoperative MRI from 2019 to 2022, and ultimately included 109 pathologically confirmed PCa patients. The Gleason score (GS) and International Society of Urological Pathology grade group (ISUP GG) were determined by two uropathologists who evaluated independently and reached a consensus. Patients were stratified based on the ISUP GG, with 42 in the pathological low-risk (PL) group (ISUP GG ≤2; 69.9±6.08 years), 67 in the pathological high-risk (PH) group (ISUP GG ≥3; 71.82±5.86 years). We also collected clinical, pathologic, and imaging data from the patients. Based on the variables screened by Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis, an improved fusion (IF) model was established and visualized with a nomogram plot. The conventional fusion (CF) model was constructed by removing the non-conventional image variables in the IF model. Model performance was evaluated using 10-fold cross-validation, receiver operating characteristic (ROC) analysis, DeLong test, and decision curve analysis (DCA). P<0.05 was considered statistically significant. Results: Significant differences were observed in the prostate-specific antigen (PSA), prostate volume (PV), Prostate Imaging Reporting and Data System (PI-RADS) scores, fat fraction (FF), T2*, and average apparent diffusion coefficient (ADC) values of the lesions between the two groups. These variables were selected to construct the IF model. The CF model was developed by removing FF and T2* values. The IF model demonstrated higher accuracy than the CF model [IF model: sensitivity =0.952, specificity =0.761, area under the curve (AUC) =0.920; CF model: sensitivity =0.762, specificity =0.761, AUC =0.819; DeLong test: P=0.002, <0.05]. Conclusions: mpMRI‑derived FF and T2* values were significantly associated with ISUP GG in PCa. Intergrating FF and T2* values with ADC, PI-RADS, PSA and PV may predict pathological risk classification more effectively.
Paravertebral blocks for post-operative analgesia for robotic-assisted partial nephrectomy: a retrospective review
Background: The interest in opiate-sparing analgesic techniques for post-operative pain management is growing. However, the use of regional analgesic techniques for robotic-assisted surgery is not well established. This study aims to assess the postoperative analgesic efficacy of a paravertebral block (PVB) on post-operative pain scores and opioid consumption in patients undergoing robotic-assisted partial nephrectomies (RAPN). Methods: This study was a retrospective analysis of patients who underwent an elective RAPN by a single surgeon from November 2018 to April 2022. A total of 200 patients (N=81 PVB, N=119 non-PVB) met inclusion criteria for further evaluation. Baseline demographics, analgesic data, and outcomes were collected. Comparisons of outcomes between the PVB and non-PVB groups were made using unadjusted and multivariable regression models appropriate for the nature of the given outcome variable (continuous, ordinal, or count). Results: There were no significant differences between the studied groups regarding age, sex, American Society of Anesthesiology classification, anesthesia type (volatile vs. total intravenous). In comparison to patients without PVB, patients with PVB showed statistically significant lower post-anesthesia care unit (PACU) morphine equivalents (β: −2.43, P=0.006), a higher floor maximum pain score [odds ratio (OR): 2.41, P=0.001], and shorter PACU length of stay (β: −16.95, P=0.002). While these findings were statistically significant, these differences were small. Conclusions: The addition of a PVB did not have a clinically significant impact on the immediate postoperative analgesic experience following RAPN.
Temporal trends, future projections, and burden of early-onset genitourinary cancers in Asia from 1990 to 2023: an analysis of the Global Burden of Disease Study 2023
Background: Early-onset cancers, often referred to as cancers that occur in those who are less than 50 years old, are indicated to be more prevalent over past decades. Significantly, early-onset genitourinary cancers could cause more burden for individuals. Asia, home to 60% of the world’s population, is undergoing a unique epidemiological transition that makes it a critical model for non-communicable disease (NCD) research. We aimed to demonstrate the incidence, burden, prediction, and risk factors of early-onset bladder cancers (EOBCa), kidney cancers (EOKCa), and prostate cancers (EOPCa) to cast light on early-onset genitourinary tumor prevention and management. Methods: We analyzed data from the Global Burden of Disease Study 2023, sourced from the Global Health Data Exchange (GHDx), covering 48 Asian countries (1990–2023). Age-standardized incidence, mortality, and disability-adjusted life-year (DALY) rates were calculated using population denominators from the United Nations. Temporal trends were quantified using the Estimated Annual Percentage Change (EAPC), with 95% uncertainty intervals (UIs) and P values derived from log-linear regression. Bayesian age-period-cohort (BAPC) modeling projected 2024–2035 incidence. Socio-demographic index (SDI) stratification and sex- and age-specific analyses were performed. Results: We found that (I) in Asia, the incidence of EOBCa [EAPC =−0.96 (95% UI: −1.15 to −0.76)] decreased from 1990 to 2023, while EOKCa [EAPC =1.40 (95% UI: 1.22–1.58)] and EOPCa [EAPC =1.50 (95% UI: 1.31–1.68)] rates increased, with EOPCa projected to continue rising; (II) the spectrum of early-onset genitourinary cancers varied across different SDI levels and countries, while EOKCa had the highest burden among the three cancer types in most regions; (III) males suffered higher risks of incidence and mortality, as well as the increasing trends for early-onset genitourinary cancers than females; (IV) tobacco was the common risk factor for these three early-onset cancers and had shown a continued upward trend between 1990 and 2023. Conclusions: (I) The declining incidence of EOBCa may reflect improved drinking water quality, whereas rising EOKCa and EOPCa incidence is likely driven by greater screening awareness, advances in imaging and biomarker-based detection, and possible overdiagnosis; (II) the increase in EOKCa may also be linked to dietary westernization; (III) the faster decline in disease burden in high-SDI regions likely results from better access to advanced treatments; (IV) early-onset genitourinary cancers exhibit substantial heterogeneity within Asia, and public health strategies should therefore be tailored to the specific epidemiologic profiles of individual countries; (V) sex differences remain evident and may involve hormone-related modulation of carcinogen metabolism; (VI) although early-onset patients are generally healthier, they still face psychological stress, fertility concerns, treatment-related sequelae, and recurrence risk. Notably, cause-specific mortality appears higher in early-onset than late-onset cases, underscoring the need for tailored public health strategies, early screening, and timely intervention.
Stem cell therapy for erectile dysfunction: a systematic review and meta-analysis
Background: Erectile dysfunction (ED) is a prevalent sexual dysfunction, and due to the limited efficacy of conventional treatments, stem cell (SC)-based regenerative approaches are being extensively investigated. We aimed to investigate the overall effect of SC therapy (SCT) on ED by consolidating findings from clinical studies and offering a general overview of the intervention content and design of these studies. Methods: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We systematically reviewed MEDLINE, PubMed, Web of Science and ClinicalTrials.gov from inception to July 26, 2024. The outcomes were analyzed using the Comprehensive Meta-Analysis software version 3.0. The Q statistic and I2 statistics were used to evaluate heterogeneity. Results: In this meta-analysis, a total of 11 studies evaluated International Index of Erectile Function (IIEF) levels, with an overall mean effect estimated at 16.872 [95% confidence interval (CI): 13.311–20.432]. The findings demonstrated statistically significant improvements in IIEF (Z=9.288, P<0.001), peak systolic velocity (PSV) (Z=5.384, P<0.001), end-diastolic velocity (EDV) (Z=4.604, P<0.001), erection hardness score (EHS) (Z=4.341, P<0.001), and resistive index (RI) (Z=22.302, P<0.001) levels. The pooled analysis demonstrated a significant improvement in IIEF-5 scores, although heterogeneity was extremely high (I2=92.59%). Furthermore, subgroup analyses revealed significant differences in patient diagnosis (z=3.29, P=0.017), baseline IIEF values (z=−3.64, P=0.003), and the type of SCs applied (z=−2.38, P=0.019). Conclusions: This study suggests that SCT may represent a promising alternative approach for the treatment of ED. However, the current evidence is primarily derived from early-phase studies characterized by small sample sizes, heterogeneous populations, lack of control groups, and short follow-up durations. Therefore, while preliminary findings indicate a potential improvement in erectile function following treatment, the overall level of certainty remains low. Further well-designed, randomized controlled trials with larger sample sizes are required before definitive conclusions can be reached and broader clinical implementation can be recommended.
Superior penile girth retention with stromal vascular fraction-enriched autologous fat grafting: a retrospective 1-year comparative study
Background: Fat resorption limits long-term outcomes of fat grafting for penile girth augmentation. Stromal vascular fraction (SVF)-enriched fat may improve graft survival by promoting angiogenesis, modulating inflammation, and via other paracrine effects. To our knowledge, no prior studies employed SVF for penile aesthetic procedures. In this retrospective non-randomized study, we aimed to assess the safety and clinical performance of SVF-enriched fat grafting versus Coleman fat. Methods: For the treatment group (n=50), protocol key steps included liposuction, non-enzymatic extraction of SVF via a novel device, fat enrichment, and graft injection, avoiding the corpora cavernosa. The Coleman fat group (n=38) received conventional grafting. Penile girth and length (flaccid and erect) and International Index of Erectile Function-5 scores were evaluated at baseline and at 1, 3, 6, and 12 months. Satisfaction was recorded at 12 months. Men with mild erectile dysfunction (n=10 and n=17 in the Coleman fat and treatment groups, respectively) also completed the full questionnaire about erection. The primary outcome was change in penile girth. Exploratory outcomes included change in penile length, erectile function, and patient-reported satisfaction with the procedure. Results: At 12 months, the treatment group showed significantly higher volume retention across all measurements (P<0.001), greater satisfaction (4.2/5 versus 3.7/5; P=0.01), and improvement of erection in mild erectile dysfunction cases (P=0.002). Changes were as follows (treatment versus Coleman fat, mean in centimeters): flaccid girth: +2.8 versus +1.6; erect girth: +1.9 versus +1.0; flaccid length: +1.0 versus +0.6; erect length: +0.8 versus +0.4. Two patients in each group had minor wound infections. Conclusions: SVF-enriched penile fat grafting improved volume retention with favourable functional outcomes in mild erectile dysfunction, supporting the feasibility of this approach in the penile setting.
Peyronie’s disease patients with pain: a post hoc analysis of the IMPRESS I/II studies
Background: Significant clinical variations exist in the definitions of acute/active vs. chronic/stable Peyronie’s disease (PD), limiting treatment options. To determine whether penile pain should inform PD treatment timing, we analyzed the association between baseline penile pain levels and treatment efficacy using data from the IMPRESS (Investigation for Maximal Peyronie’s Reduction Efficacy and Safety Studies) I/II studies of collagenase clostridium histolyticum (CCH). Methods: A post hoc analysis of pooled data from 2 phase 3 randomized double-blind trials of CCH in PD (IMPRESS I, NCT01221597; IMPRESS II, NCT01221623) was conducted. CCH-treated participants were stratified by baseline penile pain levels using investigator-assessed and patient-reported measures. A subgroup analysis stratified participants with Any Pain by disease duration. Results: At total of 364 CCH-treated men were included. Mean penile curvature improvements at week 52 were similar across all 4 investigator-assessed and patient-reported penile pain measures (35.0–36.7% improvement for the No Pain group vs. 32.2–33.9% improvement for the Any Pain group, P=0.14–0.65). Among those experiencing Any Pain, no statistical differences were observed in men with shorter (12–18 months; 21.8–34.8% improvement) vs. longer (>18 months; 31.4–36.8% improvement, P=0.20–0.95) disease durations. Conclusions: Men with PD who were treated with CCH experienced similar curvature improvements regardless of baseline pain status or disease duration among those who experienced any pain. Findings support the literature that demonstrate similar efficacy when treating men with active vs. stable disease, suggesting that ongoing pain is not a contraindication to CCH therapy.
From pharmacological management to regenerative medicine: a bibliometric analysis of global trends and evolutionary patterns in diabetic bladder dysfunction (2000–2024)
Background: Diabetic bladder dysfunction (DBD) is a prevalent complication of diabetes that severely impacts quality of life. Conventional treatments have long been confined to managing downstream symptoms with minimal efficacy in advanced stages. This study employs systematic bibliometric analysis to comprehensively map the knowledge foundations, evolving research hotspots, and future translational trajectories in global DBD research spanning 2000 to 2024. Methods: A comprehensive search was conducted on the Web of Science Core Collection (WoSCC) for literature published between January 1, 2000, and August 8, 2024. To maximize the elimination of “noise” data typical of automated retrievals, a rigorous two-stage manual full-text screening process was employed, ultimately yielding 264 high-quality core original articles. Bibliometric tools, including CiteSpace and VOSviewer, were utilized to perform visual analyses of country/institution collaboration networks, citation bursts, and keyword timelines. Results: Over the past 25 years, the publication volume in the DBD field has exhibited a fluctuating upward trajectory. The global research landscape has evolved from the absolute dominance of U.S. in the early stages to a multipolar collaborative network that now includes China, Greece, and Germany. Keyword timeline clustering revealed a clear three-phase paradigm shift: the early phase (2000–2010) focused on physiological characterizations and symptomatic management (e.g., ‘muscarinic receptors’, ‘smooth muscle’); the intermediate phase (2010–2018) delved into upstream core pathological mechanisms (e.g., ‘oxidative stress’, ‘hypoxia’, ‘autonomic neuropathy’); and the recent phase (2019–2024) witnessed the sudden emergence of novel hot clusters such as ‘defocused low-energy shock wave’ and ‘regeneration’. Conclusions: DBD research is undergoing a transition from pharmacological symptom control to regenerative repair targeting the underlying pathologies. Emerging physical-biomodulatory therapies, represented by low-energy shock waves, offer new hope for reversing the decompensation stage of bladder dysfunction. Future research urgently requires large-scale randomized controlled trials to advance the clinical translation of these regenerative medicine strategies.
Comparative outcomes of minimal-incision versus standard hydrocelectomy: reduced bleeding and healthcare utilization in a multi-surgeon cohort
Background: Hydrocelectomy is one of the most commonly performed benign scrotal procedures, but postoperative complications such as hematoma, infection, and wound-related issues remain common.Minimally invasive approaches to hydrocelectomy may reduce perioperative morbidity and healthcare utilization. Minimally invasive approaches may reduce perioperative morbidity and postoperative healthcare utilization. The minimal-incision modified fenestration technique (MIMFeT), performed under local anesthesia, has not been evaluated in a multi-surgeon, real-world setting. We conducted a retrospective cohort study comparing outcomes of MIMFeT vs. standard hydrocelectomy. Methods: We retrospectively reviewed 313 patients who underwent hydrocelectomy [2018–2024]. Patients underwent either MIMFeT or standard hydrocelectomy based on surgeon preference. The primary outcome was 30-day postoperative complications (bleeding, infection, and/or reoperation). Secondary outcomes included unplanned postoperative healthcare utilization and recurrence. Results: Among 313 patients (132 MIMFeT; 181 standard), overall complication rates were lower with MIMFeT (6.1% vs. 13%, P=0.057). Bleeding occurred in 6.1% of standard cases and 0% of MIMFeT cases (P=0.003). Rates of infection and reoperation were similar between groups. Patients undergoing MIMFeT also experienced significantly fewer unplanned postoperative patient contacts, including phone calls, portal messages, and clinic visits (43% vs. 59%, P=0.01). One-year recurrence rates were similar between groups. Conclusions: When compared to standard hydrocelectomy technique, MIMFeT provides comparable efficacy with elimination of bleeding events and reduced postoperative healthcare utilization. These findings support MIMFeT as a particularly advantageous option for patients at elevated bleeding risk and as a scalable, office-based alternative to standard hydrocelectomy that may improve patient outcomes while reducing healthcare resource utilization.
Safety and effectiveness of a modified technique for three-piece inflatable penile prosthesis implantation under local anesthesia with a minimal scrotal incision (Wang’s incision) in the treatment of erectile dysfunction
Background: Erectile dysfunction (ED) is a common disorder in adult males that can seriously affect quality of life. For patients with moderate-to-severe ED who are unresponsive to first- or second-line treatments [e.g., oral phosphodiesterase type 5 (PDE5) inhibitors], penile prosthesis implantation (PPI) is the definitive treatment recommended by international guidelines. Conventional PPI is usually performed under general or spinal anesthesia and requires a relatively long incision, resulting in substantial trauma. Consequently, it may not be suitable for elderly patients or those with underlying comorbidities. The present study was designed to evaluate the safety, feasibility, and clinical effectiveness of a modified technique for three-piece inflatable penile prosthesis (IPP) implantation under local anesthesia with a minimal scrotal incision, which we term Wang’s incision. Methods: A retrospective analysis was conducted on 220 patients who underwent AMS 700TM three-piece IPP implantation between January 2022 and December 2025 and completed the 2-year postoperative follow-up. Patients were divided into a control group (n=118, general/spinal anesthesia) and a modified group (n=102, local anesthesia with Wang’s incision). Perioperative parameters, pain scores [based on the Numeric Rating Scale (NRS)], erectile function, and patient satisfaction were compared between the groups. Results: The modified group showed significantly shorter cylinder placement time, total operative time, and incision length compared to the control group (all P<0.01). Intraoperative pain scores remained within the tolerable range, peaking during reservoir placement (4.51±1.72). Both groups demonstrated significant improvements in erectile function and patient satisfaction postoperatively (both P<0.01), with no significant intergroup differences observed. In the modified group, no cases required conversion to general or spinal anesthesia, and no serious complications occurred. Conclusions: The modified local anesthesia technique with Wang’s incision is safe and effective for three-piece IPP implantation. It has several advantages, including minimal invasiveness, short operative time, rapid recovery, and improved cosmesis, making it particularly suitable for elderly patients or those with comorbidities who are unfit for general or spinal anesthesia.
Long non-coding RNA (lncRNA) XIST drives TGF-β-induced renal cancer progression via miR-141-3p/ZEB1 signaling
Background: Long non-coding RNA (lncRNA) X inactive-specific transcript (XIST) is linked to tumor metastasis; however, research on its role in renal cancer (RC) is limited. This study investigated the function and underlying mechanism of XIST in RC. Methods: After transforming growth factor beta (TGF-β) stimulation of 786-O and Caki-1 cells, morphological changes were assessed by microscopy, and XIST expression was quantified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). XIST-microRNA-141-3p (miR-141-3p) and miR-141-3p-zinc-finger E-box binding protein 1 (ZEB1) interactions were validated by dual-luciferase reporter assays. Cells were then transfected with small interfering (si)-XIST alone or combined with miR-141-3p inhibitor, followed by analyses of: (I) XIST and miR-141-3p expression; (II) cellular morphology; (III) proliferation [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay]; (IV) apoptosis (flow cytometry); (V) epithelial-mesenchymal transition (EMT) markers (N-cadherin, Vimentin, and Snail) and E-cadherin (western blot/immunofluorescence); and (VI) migration and invasion (Transwell assays). ZEB1-mediated rescue of miR-141-3p mimic effects was similarly examined. Results: TGF-β triggered EMT in RC cells and elevated XIST expression. XIST knockdown suppressed proliferation, EMT, migration, and invasion, while promoting apoptosis in TGF-β-stimulated cells. Mechanistically, XIST sponged miR-141-3p, and miR-141-3p inhibition partially rescued the phenotypic effects of XIST silencing. Additionally, ZEB1 was identified as a miR-141-3p target, and ZEB1 overexpression reversed the miR-141-3p mimic-mediated suppression of TGF-β-induced malignant behaviors. Conclusions: These findings establish the XIST/miR-141-3p/ZEB1 axis as a regulator of TGF-β-driven proliferation and metastasis in RC in vitro.
Feasibility and early outcomes of single-port robotic-assisted radical cystectomy with intracorporeal ileal conduit: an initial Spanish case series
Background: Single-port robotic-assisted radical cystectomy (SP-RARC) with intracorporeal urinary diversion (ICUD) represents a novel, minimally invasive approach for the surgical management of muscle-invasive bladder cancer (MIBC). While its feasibility has been demonstrated in high-volume centers, clinical experience remains scarce. We report the first Spanish experience with SP-RARC and ICUD, including perioperative outcomes and early postoperative results. Case Description: A prospective case series registry including the first four patients who underwent SP-RARC with ICUD between April and June 2025 was conducted. All procedures were performed by a single high-volume robotic multiport surgeon using the da Vinci SP® platform. Surgical steps postoperative management and early outcomes were standardized and recorded. All procedures were successfully completed using a single-port approach, without conversion to multiport or open surgery. No intraoperative complications occurred. The mean operative time was 249 minutes, with a mean estimated blood loss of 500 mL, a mean lymph node yield of 18.5, and a mean hospital stay of 6 days. Two patients (50%) experienced minor postoperative complications (Clavien-Dindo grade I–II); one required readmission for intravenous antibiotic therapy due to a febrile urinary tract infection. Final pathology revealed pT4aN0, pT1N0, pT3aN0 and pT4aN1. Surgical margins were negative in all cases. Conclusions: SP-RARC with intracorporeal ileal conduit reconstruction was technically achievable in this initial case series when performed at an experienced robotic center. Given the limited cohort size and short follow-up, these findings should be interpreted as preliminary feasibility data requiring further validation in larger multicenter studies.
Robot-assisted vesical mucosal graft ureteroplasty: a novel technique using an autologous tissue substitute for ureteral reconstruction
Ureteroplasty using autologous grafts or flaps has emerged as an important reconstructive option for complex proximal or mid-ureteral strictures. Among available tissues, vesical mucosa may be a promising graft material because it is covered by urothelium, readily available, and well adapted to the urinary environment. This study aimed to present our surgical technique and perioperative outcomes of robot-assisted vesical mucosal graft (VMG) ureteroplasty for a mid-ureteral stricture. A 36-year-old woman with progressive left hydronephrosis was admitted to our hospital after failed prior endourological management. Preoperative antegrade and retrograde pyelography demonstrated an approximately 5-cm stricture in the left mid-ureter. In addition, the patient was scheduled to undergo dental implantation, making oral mucosal graft harvest less desirable. Robot-assisted VMG ureteroplasty was therefore performed. The procedure consisted of four main steps: identification of the ureter and longitudinal incision of the stricture segment; harvesting and ex vivo tailoring of the VMG; double-J stent placement and ventral onlay anastomosis; and mesenteric fat wrapping of the graft with closure of the bladder incision. During graft preparation, the serosal and muscular layers were removed, and the submucosal tissue was carefully thinned while preserving the lamina propria as much as possible. A previously reported “two-point” fixation technique was used to stabilize the VMG during anastomosis, and indocyanine green was administered intravenously to confirm satisfactory perfusion before suturing. The procedure was completed successfully in 146 minutes, with an estimated blood loss of 10 mL. Postoperative hospital stay was 5 days, and no perioperative complications occurred. During 6 months of follow-up, the patient remained asymptomatic, renal function was stable, and computed tomography showed improvement of hydronephrosis. In conclusion, robot-assisted VMG ureteroplasty appears to be a safe and feasible option for selected patients with mid-ureteral stricture. Larger series and longer follow-up are needed to further validate this technique.
Varicocelectomy in men with varicocele-associated infertility: a narrative review of semen quality and reproductive outcomes
Background and Objective: Varicoceles, defined as an abnormal dilation of the pampiniform venous plexus within the scrotum, are considered the most common surgically correctable cause of male infertility. Yet, it remains unclear exactly how to best select patients for the procedure and how the different surgical methods compare in practice. While prior reviews have established the general benefits of varicocelectomy, there is a clinical need to synthesize recent data on emerging molecular markers like sperm DNA fragmentation, alongside conventional parameters and final reproductive outcomes. The objective of this review is to evaluate the effects of varicocele repair on overall semen quality and male fertility outcomes, while comparing the safety and efficacy of different surgical approaches. Methods: A literature search was conducted across the PubMed and Embase databases for English-language clinical trials published between January 2010 and April 2026. Studies were eligible if they evaluated adult men undergoing varicocelectomy and reported quantitative postoperative data on semen parameters, pregnancy rates, or surgical complications. The extracted data were qualitatively synthesized to provide a broad clinical overview of treatment efficacy. Key Content and Findings: A total of 24 core clinical trials were included in the primary analysis. The synthesized evidence demonstrates that varicocelectomy significantly improves conventional semen parameters and reduces molecular damage. Microsurgical techniques consistently outperformed laparoscopic and open methods, offering the highest spontaneous pregnancy rates and the lowest incidence of complications. The literature reveals ongoing inconsistencies regarding the optimal management of subclinical contralateral varicoceles, with varying reproductive outcomes reported across different cohorts. Conclusions: Varicocelectomy is an effective method for treating male infertility, leading to improved semen quality and increased chances of natural conception. Microsurgical varicocelectomy remains the method of choice due to its highest efficacy and lowest complication rate. Current literature is still limited by varied methodologies and inconsistent reporting of long-term reproductive outcomes. Debate also continues regarding the exact extent of surgery needed in bilateral or subclinical cases. Future trials should use standard outcome measures and group patients by specific baseline characteristics to help tailor treatments to individual patients.
The role of Piezo1 as a mechanotransduction hub in bladder fibrosis: therapeutic targeting strategies and challenges—a narrative review
Background and Objective: Bladder fibrosis represents an irreversible pathological endpoint in various urological disorders, including neurogenic bladder (NGB) and partial bladder outlet obstruction (PBOO), leading to severe voiding dysfunction. Current therapies fail to reverse established fibrosis, highlighting the urgent need for upstream therapeutic targets. This review aims to synthesize current knowledge on the role of Piezo1, a mechanosensitive ion channel, as a central mechanotransduction hub in bladder fibrosis pathogenesis, and to evaluate potential therapeutic strategies targeting this channel. Methods: We conducted a comprehensive literature search of PubMed, Web of Science, and Scopus databases for studies published between January 2010 and June 2026 examining Piezo1’s role in bladder pathophysiology, mechanotransduction, and fibrotic mechanisms. Key Content and Findings: Piezo1 directly translates pathological pressure overload into intracellular signals through Ca2+ influx, triggering fibroblast activation and myofibroblast differentiation. Piezo1 activation synergistically activates pro-fibrotic TGF-β1/Smad and Hippo/YAP1 pathways—key drivers of fibrosis progression. However, therapeutic targeting faces significant challenges due to Piezo1’s vital physiological roles in cardiovascular pressure sensing and renal fluid homeostasis, raising off-target risks with non-selective inhibition. Emerging strategies include allosteric modulators targeting unique Piezo1 domains, local intravesical delivery systems, and targeting Piezo1-interacting regulatory proteins to block pathological signaling while preserving physiological functions. Conclusions: Piezo1 represents a novel upstream therapeutic target for bladder fibrosis. Future “smart” therapeutics targeting Piezo1-specific pathological signaling while preserving physiological functions offer new hope for end-stage bladder diseases. Further research on Piezo1-specific modulators and interactome mapping is warranted.
Guideline of guidelines: a scoping review on comparison of major clinical guidelines for erectile dysfunction
Background: There are numerous published societal guidelines for the management of men with erectile dysfunction (ED), often with specific nuances and some variations in diagnostic and treatment strategies based on relevant locoregional factors such as sociocultural barriers and differences in emphasis between urological organisations versus sexual medicine societies. This “guideline of guidelines” narrative format will enable clinicians to identify best clinical practices, standardize the delivery of healthcare and address any inconsistencies so that future research can be undertaken to improve ED care pathways. Methods: The review was conducted as a scoping review with a structured comparison of international clinical practice guidelines for the assessment and management of ED. Guidelines were identified through searches of official websites of major urological organisations and sexual medicine societies and published literature, with further review of references within each guideline. A total of eleven national and international ED guidelines were selected for inclusion in this study. Results: Although first-line pharmacotherapy is well established, recommendations for patient assessment, investigation and further treatment differ across various guidelines. There was a wide consensus in the evaluation of men with ED, especially concerning cardiovascular risk assessment. Divergence was noted in testosterone screening thresholds, adoption of a stepwise management approach and sequencing of intracavernosal injection and vacuum erection device therapy in the treatment algorithm. While there is substantial agreement among the guidelines in assessment and core management principles, meaningful variation exists in testosterone testing thresholds, endocrine evaluation and therapeutic sequencing. Conclusions: Clinicians need to be mindful of existing discrepancies (and similarities) among these major ED guidelines and to adapt specific nuances and tailor critical aspects of these guidelines based on locoregional factors and personalize the care in the ED model specifically to the individual patient.
Effects of GLP-1 analogs on metabolic alterations including male sexual function, hypogonadism and erectile dysfunction: a narrative review
Background and Objective: Metabolic alterations in chronic diseases such as dyslipidemia, type 2 diabetes mellitus (T2DM), and obesity disrupt hormonal regulation and perpetuate inflammation and oxidative stress across multiple systems, including the reproductive system. Focusing on the physiological functions of glucagon-like peptide-1 (GLP-1) and the organ-wide effects of its analogues, this review clarifies their mechanisms of action and long-term consequences, particularly regarding weight loss, oxidative stress, inflammation, and endothelial dysfunction. Methods: A narrative literature search was performed in PubMed, Science Direct, and Web of Science databases, with the search date set on March 20, 2026 using Medical Subject Headings (MeSH) terms such as GLP-1, GLP-1RA, obesity, male sexual dysfunction, and employing the Boolean operators “AND” and “OR” to retrieve relevant information about metabolic syndrome, body mass index (BMI), male infertility, endothelial dysfunction, hypogonadism and erectile dysfunction (ED). Key Content and Findings: The primary emphasis is on the impact of GLP-1 analogs in obesity, highlighting their potential for treating hypogonadism and ED, and establishing their role as a therapeutic approach that addresses key mechanisms underlying metabolic and reproductive pathology. This review examines how GLP-1 analogue treatment, initially developed for T2DM, is now being extensively repurposed for patients with obesity to address these systemic metabolic disturbances, and also examines its effect on male sexual function, ED hypogonadism, and infertility. Conclusions: Even though these drugs were initially administered to improve metabolic control in patients with T2DM, numerous studies have demonstrated that the beneficial effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) extend beyond glucose and weight control, including positive effects on male sexual and reproductive functions.
Penile skin necrosis after complex penile surgery with synthetic grafts: a case report
Background: Severe complications following complex penile reconstructive surgery are uncommon but may be devastating, particularly when synthetic grafts are employed. Infection and progressive penile skin necrosis can rapidly compromise erectile structures and functional outcomes. Evidence guiding the optimal management of extensive necrosis after graft-based augmentation procedures remains limited. We report a case of severe penile skin necrosis following complex penile surgery with synthetic graft implantation, highlighting a staged salvage strategy aimed at infection control and preservation of erectile anatomy. Case Description: A 36-year-old man presented with progressive penile skin necrosis and infection after undergoing corrective penile surgery at an external centre, including plaque excision, bilateral placement of Gore-Tex® grafts, suspensory ligament section, circumcision, and vasectomy. Clinical evaluation revealed extensive cutaneous necrosis with partial exposure of synthetic grafts. Urgent surgical exploration was performed, consisting of radical debridement and complete graft removal. The corpora cavernosa were exposed but viable and intentionally left uncovered as part of a staged reconstructive approach. Targeted antibiotic therapy and adjunctive hyperbaric oxygen treatment were initiated. After infection control and wound stabilization, definitive reconstruction was achieved using a split-thickness skin graft combined with a dermal regeneration template (Matriderm®). The postoperative course was uneventful, with excellent graft take and satisfactory cosmetic results. Conclusions: Extensive penile necrosis following synthetic graft-based surgery requires prompt recognition and aggressive management. Early removal of foreign material, radical debridement, and a staged reconstructive strategy are essential to prevent further tissue loss and preserve erectile structures. Multidisciplinary management and the use of dermal regeneration templates may facilitate reliable coverage and favourable functional recovery in complex salvage scenarios.
Erratum: Enzalutamide-resistant related lncRNA NONHSAT210528 promotes the proliferation and invasion of prostate cancer
Erratum: Nomogram for predicting acute kidney disease in patients with upper tract urothelial carcinoma undergoing adjuvant chemotherapy following radical nephroureterectomy